Summary Improving the durability and efficacy of the antibody response induced by novel influenza vaccines, and generating novel anti-influenza therapeutic reagents are central goals of influenza research. A more durable influenza vaccine and broad-spectrum therapeutics are important for protection against mutant and novel influenza strains that cause annual infection and pandemics. Monoclonal antibodies (mAbs) have provided major advances both in our thinking and for design of more broadly-protective vaccines and as potential broad- spectrum anti-influenza therapeutics. While hemagglutinin (HA) remains a mainstay as a vaccine or therapeutic target, antibodies to neuraminidase (NA) and other influenza proteins are much less studied but are also protective and may bind a wider range of influenza strains. In the various projects of this program mAbs against influenza HA, NA, matrix protein (M1) and nuclear protein (NP) will be used to identify epitopes, to evaluate known and novel epitopes for breadth and potency of protection, to learn new mechanisms of protection, and to evaluate trial vaccine efficacy. Thus the four projects in this program will use the mAb core as a central resource in order to inform on antigen and vaccine design. Further, the studies proposed will generate large panels of mAbs that may themselves be valuable as therapeutic reagents to treat influenza infections. For this we will produce antibodies from novel cohorts that we have identified that preferentially target conserved epitopes on HA, and at substantially greater frequencies to conserved epitopes on other influenza proteins including NA, NP and M1. The core will also help the projects evaluate trial vaccine efficacy and specificity at the monoclonal antibody level.